^ 293023 A7 B7 經濟部中央梯準局貞工消費合作社印製 五、發明説明（1 ) 發明背景 發明領域 本發明係有關適用於塑膠之新穎苯幷咪唑-2-胺基甲 酸院基醋化合物及其製法，以及其作爲一抗菌劑的用途。_ 先前技藝之描述 下列式丨丨所代表之苯幷咪唑-2-胺基甲酸甲酯以萁俗 名"Carbendazim"(以下簡稱爲CBZ)而廣爲知悉。美 國專利3,010,968號敎導了 CBZ爲一具有低毒性 (LD5〇 = 6800 mg/k g鼠）之抗菌劑，其用途廣泛例 如用於油漆、電氣零件及塑膠製品。 當一具有抗細菌活性之有機物例如CBZ被添加於塑 膠製品（包括聚乙烯或聚丙烯）時，其會有留失現象而導致 該塑膠製品之抗菌活性迅速降低。吾人相信此現象係因爲 該有機抗菌劑與塑膠之相容性低的關係。 發明要旨 於是本發明之一主要目的即在提供新穎的抗菌化合物 其可克服先前技藝所遭遇的問題，該抗菌化合物與塑膠具 有好的相容性並且具有優異的抗菌活性。 本發明的另一目的在提供一種製備該適用於塑膠的新 穎抗菌劑的方法。 本發明的特徵在於提供具有下列式I的苯幷咪唑 - 2 -胺基甲酸烷基酯化合物： -3 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 請 先 閱 讀 背 ί； 冬 事〆 3 再 寫 本 頁 訂 、'求 A7 B7 五、發明説明（2 )^ 293023 A7 B7 Printed by the Zhenggong Consumer Cooperative of the Central Bureau of Economic Development of the Ministry of Economic Affairs 5. Description of the Invention (1) Background of the Invention Field of the Invention The present invention relates to novel benzimidazole-2-aminocarbamate-based vinegar compounds suitable for plastics and Its preparation method and its use as an antibacterial agent. _ Description of prior art The methyl benzimidazole-2-aminocarbamate represented by the following formula is widely known under the common name " Carbendazim " (hereinafter referred to as CBZ). US Patent No. 3,010,968 introduced CBZ as an antibacterial agent with low toxicity (LD50 = 6800 mg / kg rat), which is widely used in paint, electrical parts and plastic products. When an organic substance with antibacterial activity, such as CBZ, is added to plastic products (including polyethylene or polypropylene), it may be lost and cause the antibacterial activity of the plastic product to decrease rapidly. I believe this phenomenon is due to the low compatibility of the organic antibacterial agent with plastic. SUMMARY OF THE INVENTION One of the main objects of the present invention is to provide a novel antibacterial compound which can overcome the problems encountered in the prior art. The antibacterial compound has good compatibility with plastics and has excellent antibacterial activity. Another object of the present invention is to provide a method for preparing the new antibacterial agent suitable for plastics. The present invention is characterized by providing a benzimidazole-2-carbamic acid alkyl ester compound having the following formula I: -3 This paper scale is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm). Please read the back first; Winter Affairs〆3 Write this page again, 'Seeking A7 B7 V. Description of the invention (2)
[I] 其中R爲具有10-24碳原子數的烷基，式I的化合物可藉 由一具有特徵的方法被製備，包含將下列式II所代表的苯 幷咪唑-2-胺基甲酸甲酯與10-24碳原子數脂肪族醇在 6〇 °C或更高的溫度及一觸媒存在下反應：[I] where R is an alkyl group having 10 to 24 carbon atoms, the compound of formula I can be prepared by a characteristic method, including the following benzimidazole-2-aminocarbamic acid represented by the following formula II The ester reacts with an aliphatic alcohol with 10-24 carbon atoms at a temperature of 60 ° C or higher in the presence of a catalyst:
NHC00CH, [II] 發明之詳細說明 式丨之新穎化合物不同於CBZ之甲基而具有一長鏈烷 ! 基單元，但仍保有抗菌活性。該長鏈烷基允許式丨之化合 物更具親脂性，因而與塑膠（聚合物）具有更佳的相容性。 經濟部中央標準局貝工消費合作社印製 依本發明，該式丨的化合物可藉將式丨丨之CBZ與 10-24碳原子數脂肪族醇在不低於60 °C的溫度及一觸媒 存在下反應而製備。於此反應中，溶劑例如二甲基亞嬾碾 或二甲基甲醯胺可以被或不被使用爲一溶媒。藉由該脂肪 醇與CBZ的酯交換反應，苯幷咪唑-2-胺基甲酸烷基酯化 合物可以被獲得，其包含相對於該脂肪醇的烷基。 鋁異丙氧化物可用作爲該脂肪族醇與CBZ的酯交換 反應的觸媒。爲了移除酯交換反應所產生之副產物，甲 -4 - 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 五、發明説明（3 ) A7 B7 醇，該酯交換反應較佳的係在一高於甲醇沸點的溫度下進 行，亦即6 0至1 5 0 0C。 將本發明製備之一塑膠樣品與一含CBZ的塑膠製品 比較可發現本發明之塑膠製品具有較佳的抗菌性及持久 性，並且優於含無機抗菌劑之塑膠製品，例如日本觸媒化 學公司（C C丨C )所販售者。 本發明可藉以下的實施例被進一步了解，該等實施例 僅作爲說明之用而非用於限制本發明》 實施例I及II分別示範式I化合物的製備（其中R爲 Ci 6，以下簡稱HCBZ)，以及使用式I化合物進行塑膠混 配（compounding)之程序。實施例III及IV描述HCBZ 的性質測試，其中實施例Μ丨測試抗菌活性而實施例I V測 試該抗菌活性的持久性。 請 先 閲 背 之 注- 意 再- 填 食 裝 訂 經濟部中央標準局員工消費合作社印製 實施例I 苯幷咪唑-2-胺基甲酸十六烷基酯化合物之製備（HCBZ: 於一配備有電磁攪拌器及短蒸餾套件之500毫升圓底 錐瓶中，加入CBZ(9.0克，50毫莫耳）、1-十六醇（30 克）及鋁異丙氧化物（100毫克），並於90°C之油浴中加熱 並攪拌18小時。同時，甲醇副產物被蒸餾出並收集於一 收集瓶中。反應進行程度藉一薄膜色層分析加予監視。當 反應溫度隨著反應終了而逐漸冷卻時，反應物變成固態。 於55 °C左右，1升的已烷被加入該反應物中，此混合物被 -5 - 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 293023 A7 jS5. 9. 30 ： B7 L——_，丨 五、發明説明（4 ) 攪拌1小時接著進行蒸餾而獲得產物。於眞空下乾燥而產 生17.5克的1~10日2:產率88%。 H-NMR分析顯示在該產物中並無殘留未反應之CBZ 或1 -己醇。 HCBZ之物理性質： 熔點：3 2 0 °C或更高（分解） H-NMR (DMSO-d6, 200 MHZ)於 80 °C 下： ppm 0.85 (3H,t), 1.2 8 (26 H,s), 1.62 (2H,t)) 4. 1 7(2H,t), 7.08 (2H,m), 7.39 (2H,m), 11.58 (1H,寬）。NHC00CH, [II] Detailed description of the invention The novel compound of formula 丨 is different from the methyl group of CBZ and has a long-chain alkyl group unit, but still retains antibacterial activity. The long-chain alkyl group allows the compound of formula 丨 to be more lipophilic, and thus has better compatibility with plastics (polymers). Printed by Beigong Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economy Prepared by reaction in the presence of a medium. In this reaction, solvents such as dimethyl sulfoxide or dimethylformamide may or may not be used as a vehicle. By the transesterification reaction of the fatty alcohol with CBZ, a benzimidazole-2-aminocarboxylic acid alkyl ester compound can be obtained, which contains an alkyl group relative to the fatty alcohol. Aluminum isopropyl oxide can be used as a catalyst for the transesterification reaction of the aliphatic alcohol and CBZ. In order to remove the by-products generated by the transesterification reaction, A-4-This paper scale is applicable to the Chinese National Standard (CNS) A4 specification (210X 297 mm). 5. Description of the invention (3) A7 B7 alcohol, the transesterification reaction is more The preferred system is carried out at a temperature higher than the boiling point of methanol, that is, 60 to 150 ° C. Comparing a plastic sample prepared by the present invention with a plastic product containing CBZ, it can be found that the plastic product of the present invention has better antibacterial properties and durability, and is superior to plastic products containing inorganic antibacterial agents, such as the Japanese Catalyst Chemical Company (CC 丨 C) The seller. The present invention can be further understood by the following examples, which are for illustrative purposes only and are not intended to limit the present invention. Examples I and II respectively demonstrate the preparation of compounds of formula I (where R is Ci 6, hereinafter referred to as HCBZ), and the procedure for compounding plastics using compounds of formula I. Examples III and IV describe the testing of the properties of HCBZ, in which Example M1 tests the antibacterial activity and Example IV tests the durability of the antibacterial activity. Please read the note on the back first-Yi Zai-Filling and Binding Example printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs I Preparation of benzimidazole-2-carbamic acid cetyl ester compound (HCBZ: In a 500 ml round-bottomed conical flask with an electromagnetic stirrer and a short distillation set, add CBZ (9.0 g, 50 mmol), 1-hexadecanol (30 g) and aluminum isopropyl oxide (100 mg), and add Heat and stir in an oil bath at 90 ° C for 18 hours. At the same time, methanol by-products are distilled off and collected in a collection bottle. The progress of the reaction is monitored by a thin-film chromatographic analysis. When the reaction temperature increases with the end of the reaction When gradually cooled, the reactant becomes a solid. At about 55 ° C, 1 liter of hexane is added to the reactant, and this mixture is -5-This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) 293023 A7 jS5. 9. 30: B7 L ——_, 丨 V. Description of the invention (4) Stir for 1 hour and then carry out distillation to obtain the product. Drying under emptiness yields 17.5 g of 1-10 days 2: Yield 88 %. H-NMR analysis shows that there is no unreacted residue in the product CBZ or 1-hexanol. Physical properties of HCBZ: Melting point: 3 2 0 ° C or higher (decomposition) H-NMR (DMSO-d6, 200 MHZ) at 80 ° C: ppm 0.85 (3H, t), 1.2 8 (26 H, s), 1.62 (2H, t)) 4. 1 7 (2H, t), 7.08 (2H, m), 7.39 (2H, m), 11.58 (1H, width).
實施例II 塑膠樣品之製備 將有機及無機抗菌劑與HDPE樹脂（韓商油公有限公 司生產，代號BD800)進行混配（compounding)。該 抗菌劑在塑膠樣品中的濃度爲1 %。於使用有機抗菌劑的 情形下，1克的CBZ與實施例丨之HCBZ分別被加入乾重 99克的基礎樹脂中，此混合物再於一Brabender Plasticasder 的 Banbury 混合器中，於 160°C 及 50 rpm下轉速下混練3分鐘。於使用無機抗菌劑的情形下， 將CCIC公司所售之內含17 % AIS抗菌劑的一母媒6克， 依上述方式與94克的基礎樹脂混練。上述含1 %抗菌劑的 塑膠混配物接著被壓縮模塑成型（190 °C下預熱5分鐘， 熟化5分鐘，及冷卻1分鐘），而製備出厚度1毫米之塑膠 本紙張尺度逋用中國國家標準（CNS ) A4规格（210Χ297>ί釐） (請先閲讀背面之注意事項再填寫本頁) 訂 經濟部中央標準局員工消費合作社印裝 7 Β 五、發明説明（5 ) 樣品，此等樣品被用於下列實施例之抗菌活性及持久性之. 測試。Example II Preparation of plastic samples Compounds of organic and inorganic antibacterial agents and HDPE resin (manufactured by Hanshang Oil Co., Ltd., code BD800) were compounded. The concentration of the antibacterial agent in the plastic sample is 1%. In the case of using an organic antibacterial agent, 1 g of CBZ and the HCBZ of Example 丨 were added to the base resin with a dry weight of 99 g respectively. Knead for 3 minutes at rpm. In the case of using an inorganic antibacterial agent, 6 g of a masterbatch containing 17% AIS antibacterial agent sold by CCIC was mixed with 94 g of base resin in the above manner. The above-mentioned plastic compound containing 1% antibacterial agent was then compression molded (preheated at 190 ° C for 5 minutes, cured for 5 minutes, and cooled for 1 minute) to prepare a plastic paper sheet with a thickness of 1 mm. China National Standards (CNS) A4 specification (210Χ297> ％) (please read the precautions on the back before filling in this page) Order the printed version of the employee consumer cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 7 Β V. Invention Instructions (5) Samples, this The samples were used for the antibacterial activity and durability of the following examples. Test.
實施例 III 含有HCBZ之塑膠樣品的抗菌活性測試 將由有利於眞菌成長之馬鈴薯澱粉葡萄糖所製成之洋 菜媒體（5毫升）混合入含有五種眞菌孢子之溶液（1毫 升），該眞菌孢子中包括黑麴菌。混合液被儲存於45 °C以 防止固化。 長寬20x30毫米之塑膠樣品以酒精消毒並置於一平 板上，接著將上述液態洋菜混合液倒於該塑膠樣品上讓其 固化。 於30 °C下培養5至7天後，觀察其上眞菌成長的情 形。眞菌成長的情形依參照一對照例而分成五級，結果列 於以下表丨及Μ中。 (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印装 表I 相對於對照例之眞菌成成速率 級數 /fr[T- 0 -20% 1 〜4 0 % 2 〜6 0 % 3 〜8 0 % 4 -10 0% 5 -7 本紙張尺度適用中國國家標準（CNS ) Α4規格（210 X297公釐） 293〇23 A7 B7 五 發明説明（6 ) 表 II 抗菌劑 眞菌成長 H C B Z 0·0(0%) CBZ 1.0 (20%) A 1 S 3.0(60%) __ 對照例 5.0 (100 % ) 經濟部中央標準局員工消費合作社印裝 表中明顯顯示出，含有1 % HCBZ之塑膠樣品在抗菌 性質上優於含有CBZ及A IS的其它樣品。 實施例IV 塑膠樣品之抗菌活性的持久性測試 將分別含有082,^1082及八丨8的三個塑膠樣品，連 同一對照例，置於一水浴中，其中循環水的溫度被維持在 5〇 °C，其中該對照例不含抗菌劑。爲了避免被洗出的抗 菌劑對塑膠樣品產生影響，所使用的循環水每天被換新。 於一預定時間後，塑膠樣品從該水浴中被取出，並以類似 於實施例丨丨丨的方式測試其抗菌性質。四周後的塑膠樣品 之抗菌活性與新鮮塑膠樣品的抗菌活性進行比較，結果列 於以下表丨U。 一 8 - 本紙張尺度適用中國國家標準（CNS )八4規格（210X297公嫠） -------II —— ^4衣--1 i __、ςτ (請先閱讀背面之注意事項再填寫本頁) Α7 Β7 893Ό23 五、發明説明（7Example III Antibacterial Activity Test of Plastic Samples Containing HCBZ The agar media (5 ml) made of potato starch glucose which is beneficial to the growth of candida was mixed into a solution (1 ml) containing five spores of candida. The fungus spores include Aspergillus niger. The mixture is stored at 45 ° C to prevent solidification. Plastic samples with a length and width of 20x30 mm were sterilized with alcohol and placed on a flat plate, and then the liquid agar mixture was poured onto the plastic sample to allow it to solidify. After incubating at 30 ° C for 5 to 7 days, observe the growth of the fungus on it. The growth of spores is divided into five levels according to a reference example. The results are shown in the following table and M. (Please read the precautions on the back before filling in this page) Printed Form I of the Employees ’Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs I The rate of success rate of mycobacteria relative to the control example / fr [T- 0 -20% 1 ～ 4 0 % 2 ～ 6 0% 3 ～ 8 0% 4 -10 0% 5 -7 This paper scale is applicable to the Chinese National Standard (CNS) Α4 specification (210 X297 mm) 293〇23 A7 B7 five invention description (6) Table II The growth of the antimicrobial agent Bacteria HCBZ 0 · 0 (0%) CBZ 1.0 (20%) A 1 S 3.0 (60%) __ Comparative Example 5.0 (100%) It is clearly shown in the printed table of the Employee Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs , Plastic samples containing 1% HCBZ are superior to other samples containing CBZ and A IS in antibacterial properties. Example IV The durability test of the antibacterial activity of plastic samples will contain three plastic samples of 082, 1082 and 8-8 respectively, and the same control example, placed in a water bath, in which the temperature of the circulating water is maintained at 50. ° C, where the control example contains no antimicrobial agent. In order to prevent the washed-out antimicrobial agents from affecting the plastic samples, the circulating water used is replaced daily. After a predetermined time, the plastic sample was removed from the water bath and tested for antibacterial properties in a manner similar to the examples. The antibacterial activity of the plastic samples after four weeks was compared with the antibacterial activity of the fresh plastic samples. The results are listed in the following table 丨 U. One 8-This paper scale is applicable to the Chinese National Standard (CNS) 8.4 specifications (210X297 public daughter) ------- II ---- ^ 4 衣 --1 i __, ςτ (Please read the precautions on the back first (Fill in this page) Α7 Β7 893Ό23 5. Description of the invention (7
表 III 時間 對照例 C B Z H C BZ A I S 新鮮 5 1 0 3 四周後 5 5 0 5 表I丨丨數據淸楚顯示出，含有HCBZ之塑膠樣品ϋ 菌性質的持久性上優於含有CBZ者。 本發明已經配合上述具體實施例被描述，熟悉本項技 藝人士將可基於以上描述作出多種變化。本發明的範圍包 括界定於下列申請專利範圍及其精神內的該等變化。 -I·ί--7 f! (請先閲讀背面之注意事項再填寫本頁) 訂 經濟部中央標準局貝工消費合作.杜印製 本紙張又度適用中國國家標準（CNS ) A4規格（210X297公釐）Table III Time Control Example C B Z H C BZ A I S Fresh 5 1 0 3 Four weeks later 5 5 0 5 Table I The data shows that the plastic samples containing HCBZ are superior to those containing CBZ in the persistence of bacterial properties. The present invention has been described in conjunction with the above specific embodiments, and those skilled in the art will be able to make various changes based on the above description. The scope of the present invention includes such changes as defined in the following patent application scope and spirit. -I · ί--7 f! (Please read the precautions on the back before filling in this page) Order the consumer cooperation of the Central Standards Bureau of the Ministry of Economic Affairs. Du printed this paper is also applicable to the Chinese National Standard (CNS) A4 specification ( 210X297mm)